# Commensal microbiota modulates ocular surface mucosal inflammation

> **NIH NIH R01** · BAYLOR COLLEGE OF MEDICINE · 2021 · $475,746

## Abstract

Sjögren syndrome (SS) is a common autoimmune disease affecting millions of patients in the US
that targets oral and ocular mucosa and their secretory glands. SS causes the most severe
aqueous deficient dry eye disease that often results in disabling eye irritation and photophobia.
There is mounting evidence that the microbiome, the community of microorganisms that inhabit
the body, has a potent immunoregulatory functions. In this proposal we seek to elucidate the
relationship between SS and the intestinal microbiota with the eventual goal of identifying
therapeutic targets within the eye and/or the microbiota with which to treat SS. Evidence suggests
that intestinal dysbiosis (microbial imbalance) contributes to the pathogenesis of SS. We
hypothesize that intestinal microbiota support maintenance of the homeostatic mucosal immune
environment and suppress desiccation-induced inflammation on the ocular surface.
Reconstitution of normal commensal microbiota would promote restoration of ocular mucosal
homeostasis. To test our hypothesis, we propose three Specific Aims: Specific Aim 1 will test the
hypothesis that among patients presenting with eye irritation, those with SS have commensal
fecal dysbiosis resulting in decreased levels of the anti-inflammatory short chain fatty acid (SCFA)
butyrate in the stool compared to patients with other types of tear dysfunction and normal control
subjects. In Specific Aim 2 we will test hypothesis that intestinal dysbiosis modulates the
inflammatory response to stress at distant mucosal sites, specifically ocular inflammation, in acute
and chronic murine models of SS. Specific Aim 3 will test the hypothesis that commensal intestinal
microbiota maintains conjunctival goblet cell density and prevents desiccation-induced goblet loss
by generating Tregs and producing SCFA butyrate.  
 Results of this proposal will have potential to demonstrate a novel new paradigm for
maintenance of homeostasis in mucosal tissues throughout the body, including the ocular surface
that has a very low abundance microbiota, by commensal intestinal microbiota and their
metabolites such as butyrate. Furthermore, they will provide rationale for a novel treatment
approach utilizing commensal fecal microbiota to enhance natural immunoregulatory
mechanisms to suppress development of mucosal autoimmune disease.

## Key facts

- **NIH application ID:** 10244985
- **Project number:** 5R01EY026893-05
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** CINTIA S. DE PAIVA
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $475,746
- **Award type:** 5
- **Project period:** 2017-09-01 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10244985

## Citation

> US National Institutes of Health, RePORTER application 10244985, Commensal microbiota modulates ocular surface mucosal inflammation (5R01EY026893-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10244985. Licensed CC0.

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